title: Inducible nitric oxide synthase as a possible target in hypertension.
abstract: Nitric oxide (NO) is an important vasodilator produced by vascular endothelium. Its enzymatic formation is derived from three different synthases: neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) synthases. While relatively small amounts of NO produced by eNOS are important to cardiovascular homeostasis, high NO levels produced associated with iNOS activity may have detrimental consequences to the cardiovascular system and contribute to hypertension. In this article, we reviewed current literature and found mounting evidence indicating that increased iNOS expression and activity contribute to the pathogenesis of hypertension and its complications. Excessive amounts of NO produced by iNOS up-regulation can react with superoxide anions forming peroxynitrite, thereby promoting nitrosative stress and endothelial dysfunction. In addition, abnormal iNOS activity can up-regulate arginase activity, allowing it to compete with eNOS for L-arginine, thereby resulting in reduced NO bioavailability. This may also lead to eNOS uncoupling with enhanced production of superoxide anions instead of NO. All these alterations mediated by iNOS apparently contribute to hypertension and its complications. We also reviewed current evidence showing the effects of iNOS inhibitors on different animal models of hypertension. iNOS inhibition apparently exerts antihypertensive effects, decreases oxidative and nitrosative stress, and improves vascular function. Together, these studies highlight the possibility that iNOS is a potential pharmacological target in hypertension.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Oliveira-Paula
authors.forename: Riccardo
authors.initials: R
authors.lastname: Lacchini
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil. tanus@fmrp.usp.br.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001119:Arginase / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D001119:Arginase